Manufacture of capsules



Feb. 29, 1944. Rw, GUNNELL y2,342,661

MANUFACTURE OF CAPSULES Filed Jan. 28, 1942 ly. e,

^ rilassante-29.11944 "2,342,661 MAUFACTI'JRE or CAPSULES Robert W. Grinnell, Hammond, Ind.' 'Application renom 28.1942', serial No. 428,515

' zooming. (ci. 117-113) This invention relatesutothe manufacture Vof capsules, andamong other objects aims'to proyide an improved method and apparatus for pro-l ducing capsules containing medicamentsor other substances. v l

'I'he nature of the invention may be readily understood by reference tol one method and apparatus embodying'tlie invention and shown in the accompanying drawing..

In said drawing: j' v Fig; 1 is an elevation indiagrar'nmatic form of a .method and apparatusv for producing capsulesv o i Fig.'2 is a plan section on the plane 2-2 `of rug-w1.l Y n y According to the illustrative method, the

medicament or other substances to be capsulated` is formed into globules or pellets comprising a measured or predetermined volume and covered with acapsule-forming nlm such as gelatin. For simplicity and convenience the term medicamen will be employedin a general senseto include whateversubstance is capsul/ated whether f.

:or\no't it is strictly a medicament.` The medicament may advantageously be in liquid form and' released in liquid globules or drops which naturally form into spherical shape, and on which a capsule is created by solidifying or otherwise setting .thereon -av-retaining nlm of coating liquid.

The expression "drops" is used in a general sense and not to' denne aspecinc amount of medicament. .In the present case, the globules are introduced into a coating liquid (such as a gelatin sol, that is, a liquid containing-gelatin) comprising the' capsule-forming material. The latter preferably has a specinc gravity greater than In the illustrative apparatus lthe medicament 'is advantageously introduced atI the lower portion lli of alreceptacle H containinginits lower portion a body of coating liquid,A such as liquid containing gelatin. Below thebody of coating liquid is a diaphragm I2 through which globules of medicament are introduced into the coating liquid. 'ln the present instance the medicament being in liquid condition, the .globules are advantageously formed by4 ejecting nxed charges of medicament through orifices i3 in the diaphragm. A temperature regulating device in'- cluding a cooling coil I4 serves to 1cool the medicament to the proper temperature and to maintain it at such temperature upon introductiono of the medicament in globule form into the coating liquid. The diaphragm advantageously incorporates insulation to prevent chilling` of the l capsule-forming liquid by the cool medicament below it. 'The lower portion I0 ofthe receptacle and the diaphragm I2 are removable from the superposed receptacle to'permit easy substitution of diaphragms to change orifice size.' For that purpose the upper and lower receptaclesarc' o flanged as at I5 and the joint between them is sealed by a gasket. Y

As shown in Fig.'2, the orifices Ilare arranged in a circular series. The orince diameter cooperates in determining the'size of the drops released. Their size and rate oi' release is advantageously controlled by a measuring pump 'I6 or othermeans, which periodically forces a predetermined volume4 of medicament through, the oriiices I 3.

If.necessary,`inorder tosecure discharge ot uni'- that of the medicament so that the globules will rise'in the liquid.' For capsulating with a thermo-plastic coating material, the globules of medicament are preferably chilled before introduction into the coating liquid and the latter is maintained at such temperature that a coating jof the liquidfwill con'geal'onthe globules as they rise. The temperature differences ,between that of 'the globules and the coating liquid depends upon the amount ofcooling necessary tocongeal an .adequate nlm of coating on the globules.

' The coated globules are removed from the capsullating material before the latter has .an opportunity to affect or impair the coating, `and thereuponthe' coating is conditioned,'in this case by cooling or chilling, so as to set or harden it suiliciently for handling. The resultant capsulesare seamless and, therefore, cannotdevelop leaks as form globules from each of the orinces, the measuring pump'may be provided with a separate measuring chamber 'and line for each orince. Generally this is not necessary since with uniform temperatures and orinces, .uniform globules will be discharged from each of the' orifices.

. The depth of the coating liquid is; adjusted towhat is necessary to congeal an adequate nlm of the globules,4 but is not great-enough to remelt or otherwise impair the coating as the globules rise through the coating liquid. In the present case the upper lever ofthe coating liquid terg inmates at dotted line l1. The capsule or nlm congealed on the globules should be'sunlciently thick and strong safely to retain the contents of the globules and to withstandq usual handling.

'I'he thickness of the nlm will .vary in case of a thermo-plastic coating with the temperature difference between the coating liquid and globule, with the size ot the globule (that-is, its heat abin theseamed capsules heretofore on the market. sorbing capacity). and with the time of immersion in the coating liquid. For gelatin coatings, the range of variation in coating liquid maybe from .005 of an inch to .030 of an inch. When the coated globules rise to the surface of the-coating liquid, they pass into a conditioning zone in 5 which the coating is set or hardened. Such conditioning zone is, in this case, represented by a supernatant layer I8 of liquid chilled substantially below the melting point of the coating and whose speciilc gravity is less than that of'the l0 coating liquid by virtue of which the conditioning liquid iioats asf a' layer upon the coating liquid. The conditioning liquid is of such character as not to dissolve or otherwise impair the gelatin or other coating or to be easily miscible with or soluble in or a solvent of the coating liquid. One form of conditioning liquid for a gelatin coating is a mixture of naphtha and carbon tetrachloride. 'I'he latter is relatively heavy and serves to adjust th'especiflc gravity of the conditioning liquid to 20 exceed that ofthe coated globules so that the latter will rise through the conditioning liquid. The adjusted specific gravity of the liquid is less f than that of the coating liquid. Neither naphtha nor carbon tetrachloride react with either the gelatin or the gelatin sol. f

The nature of the coating liquid determines the character of .the conditioning liquid I il whose function is to treat or condition the coating for handling. In the present case, the coating is 30 conditioned merely by cooling.

'I'he depth of the column of conditioning liquid is substantial as compared with that of the coating liquid so as' adequately to harden or toughen thecoating for handling.

When the coated globules reach the surface of the conditioning liquid, they may be either manually or mechanically removed. In the present instance they flow over a Weir I9 and roll down an inclined perforated drain board to drain oi any adhering cooling liquid into a receptacle 2|. A circulating pump 22 advantageously maintains a circulation or upward current of the cooling liquid both to maintain the column of cooling liquid at the desired low temperature and also to carry the capsules over the Weir. A temperature-regulating coil 23 located in the receptacle 2i re-cools the cooling liquid to a predetermined temperature. v

Coating liquid issupplied through conduit 24 50 from a lconstant level reservoir-25. Conduit 24 leads to a header having a series of orifices 26 around the space Il so that fresh coating liquid i will enter the space Il without causing undue turbulence. The header may advantageously act` as a jacket around the coating liquid topreyent loss of heat through the sides oi the reeptable. The coating liquid is heated by heating element 21 controlled by thermostat 28 located adjacent.

the entry of the coating li uid into the rece tacle. .60

q p fcoating and conditioning liquid may be used.

column of coating liquid balancesthe combined head of coating liquid and conditioning liquid in receptacle Il. Since the volume of the latter is maintained constant, a reduction of the coating liquid in receptacle Il results in flow of coating liquid from conduit 24 into receptacle Il. Coat- 75,

ingliquid is supplied to reservoir 25 from storage tank 30. The level oi' the reservoir 25 is maintained constant by the overflow 3| and by adjust ing the valve 32 `from tank M to feed coating liquid at a rate sumcient to keepreservoir illled to overflowing. A stirring device 33 circulates the liquid around the heating element 21. Tank B is preferably supplied with a heater 3l to pref vent congealing of the coating.

To prevent undue cooling or congealing of the coating liquid at the inter-face I1 between tLilie coating liquid and the lcooling liquid, hea g meansin the form ofan electric heater coil 35 is advantageously located at the inter-face and serves to prevent the cooling liquid from unduly lowering. the temperature of the coating liquid at theinter-face. The coating liquid is maintained in such uid 'condition at theinter-face that rising of the coated globules through the inter-face is not restrained and appendages or tails of coating material are not dragged' along with the globules. n by its lead-in conduit and is preferably positioned out of the'vertical linesof travel of the globules (see FigL2).

Cooling liquid adjusted to the proper tempera..-

v Percent Gelatin 0f 150 to 250 B100m 25 Glycerine 15 Water .60

A depth of about two inches'of such liquid in receptacle I I at-about degrees Fahrenheit will develop a satisfactory gelatin coating onV threey minim globules of cod liveroil introduced at a temperature of about 12 degrees Fahrenheit. 'I'he glycerine functions .as a so-called plasticizer to prevent the capsule from becoming too brittle. Gelatin ot a` wide rangeoi' quality may be used. However,A the Vpoorer the quality the higher the gelatin concentration required in the sol and the poorer the quality of coating. Superior results are obtained by the use of gelatin of from to 300l3iloom. The temperature `of the gelatinsol in the receptacle should be from 90 to 100 degrees Fahrenheit and that of the conditioning liquid for gelatin capsules of from 40to 60 degrees Fahrenheit.rv

It will be understood that various types of Preferably, they should have the, following properties. v v

1. The coating liquid should be heavier than the medicament and should form a coating thereon as the globules of medicament rise' through it.

2. The conditioning liquid should:

1 a. Properly condition the coating to toughen it; f 1 b. Be lighter in weight than the coating liquid butlheaviervthan the medicament; c. Not' dissolve or otherwise impair' the coating nor should it be miscible with or readily soluble in the coating liquid.

The heating coil is supported liquid adjacent said inten-faceta prevent congealing at the inter-face, and means for cooling the upper vportion of the cooling liquid. y

T17.' Apparatus for forming capsules comprising in combination a receptacle having .therein a body of liquid coatings.v solution 'and a superposed layer of cooling liquid, an orifice adjacent thel I in combination a receptaclehaving therein a body of liquid coating solution and a superposed layer of cooling liquid, an 'orillce adjacent the 'lower portion of the coating liquid, lneans for introducing small quantities 'of liquid periodically through said orifice and means at the inter-lace between the coating liquid and-the cooling liquid for elevating the temperature of the cooling liquid adjacent said inter-face to prevent congeallng at the inter-face,.and means for regulating the temperature of the c oating liquid to maintain it in liquid condition.

19. Apparatus for forming capsules comprising in combination la receptacle having therein a body oi' liquid coating solution and a superposed layer oi cooling liquid, an oriilce adjacent the lower portion of the coating' liquid, means for introducing small quantities of liquid periodically adjacent said inter-face to prevent conge'aling at the inter-face, means for regulating thel teml'. perature of the coating liquid to maintain it in liquid condition, and means for circulating and ycooling the upper portion of said cooling liquid.

1 20. Apparatus for forming capsules or the like comprising in combination a receptacle having f 

